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Indian Journal of Dermatology 2024Lichenoid drug eruption (LDE) is an uncommon cutaneous adverse drug reaction, where a variety of drugs used in day-to-day clinical practice have been implicated.
BACKGROUND
Lichenoid drug eruption (LDE) is an uncommon cutaneous adverse drug reaction, where a variety of drugs used in day-to-day clinical practice have been implicated.
OBJECTIVE
To describe the clinico-demographic characteristics of patients with LDE and to identify the most likely drugs involved.
METHODS
In this prospective, observational study, consecutive patients with LDE presenting to the dermatology department of a tertiary teaching hospital were included. The clinico-demographic profile of patients with LDE and implicated drugs was noted. Treatment of drug reaction along with outcome was also documented. Naranjo adverse drug reaction probability scale was used for causality assessment of the drug reactions. A thorough literature review on LDE was also undertaken due to the paucity of existing literature.
RESULTS
A total of 15 patients (11 males and 4 females) with LDE were evaluated. Their age ranged from 37 to 61 years, with a mean of 51.53 ± 7.59 years. Anti-hypertensive medications (40%) were the most common culprit agent, followed by antitubercular drugs (33.4%), anti-diabetic agents (13.3%), and others (13.3%). The latent period (time from drug initiation to the appearance of a cutaneous eruption) varied from 15 days to 6 months (mean 2.2 months). Cutaneous involvement was generalized in 73.4% and photo-distributed lesions in 26.6%. Drug provocation test was done to identify the culprit drug. According to the Naranjo adverse drug reaction probability scale, one-third of LDEs were "definite," whereas two-thirds were designated as "probable."
CONCLUSION
LDE is more common in the elderly population. The latent period is comparatively longer in LDE than in other common drug reactions. Prompt recognition and withdrawal of suspected drug are essential to minimize disease morbidity.
PubMed: 38841229
DOI: 10.4103/ijd.ijd_878_23 -
PloS One 2023The casts of Pompeii bear witness to the people who died during the Vesuvius 79 AD eruption. However, studies on the cause of death of these victims have not been...
The casts of Pompeii bear witness to the people who died during the Vesuvius 79 AD eruption. However, studies on the cause of death of these victims have not been conclusive. A previous important step is the understanding of the post-depositional processes and the impact of the plaster in bones, two issues that have not been previously evaluated. Here we report on the anthropological and the first chemical data obtained from the study of six casts from Porta Nola area and one from Terme Suburbane. A non-invasive chemical analysis by portable X-ray fluorescence was employed for the first time on these casts of Pompeii to determine the elemental composition of the bones and the plaster. Elemental profiles were determined providing important data that cross-referenced with anthropological and stratigraphic results, are clearly helpful in the reconstruction of the perimortem and post-mortem events concerning the history of these individuals. The comparative analyses carried out on the bone casts and other collections from burned bones of the necropolis of Porta Nola in Pompeii and Rome Sepolcreto Ostiense, and buried bones from Valencia (Spain), reveal the extent of high temperature alteration and post-depositional plaster contamination. These factors make bioarchaeological analyses difficult but still allow us to support asphyxia as the likely cause of death.
Topics: Humans; Animals; Splints; Anthropology; Asphyxia; Chromatography, Gas; Drug Contamination; Lepidoptera; Nitroarginine
PubMed: 37610984
DOI: 10.1371/journal.pone.0289378 -
Scientific Reports Aug 2023Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatological emergencies. The role of cytokines and chemokines in the pathogenesis,...
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatological emergencies. The role of cytokines and chemokines in the pathogenesis, progression of the disease, and histopathologic features is not fully elucidated. To address this gap, we conducted a retrospective study examining the associations between 42 serum biomarkers, histopathologic findings, and clinical outcomes in SJS/TEN patients. We reviewed the medical records of 23 patients diagnosed with SJS/TEN. Regarding histopathology, our study did not reveal any significant associations between the degree of epidermal necrosis, dermal mononuclear cell infiltration, and clinical outcomes. However, an intriguing observation was made regarding the degree of dermal infiltration of CD8 + cells, which showed a negative correlation with the severity of acute ocular complications. Notably, serum levels of IFN-γ positively correlated with the number of CD8 + cells in dermal infiltration. Additionally, higher serum levels of myeloperoxidase were associated with greater degrees of epidermal necrosis, while serum Fas ligand and stem cell factor levels were elevated in individuals with increased dermal mononuclear cell infiltration. Furthermore, the levels of S100A8/A9 were significantly correlated with the SCORTEN and mortality rate. These findings provide insights into the intricate pathogenesis of the disease.
Topics: Humans; Calgranulin A; CD8-Positive T-Lymphocytes; Necrosis; Retrospective Studies; Stevens-Johnson Syndrome
PubMed: 37604858
DOI: 10.1038/s41598-023-40812-3 -
European Journal of Case Reports in... 2023IgA vasculitis and hypersensitivity reactions following exposure to non-steroidal anti-inflammatory drugs (NSAIDs) are very rarely associated with purpura fulminans...
BACKGROUND
IgA vasculitis and hypersensitivity reactions following exposure to non-steroidal anti-inflammatory drugs (NSAIDs) are very rarely associated with purpura fulminans (PF). The latter is a coagulation event characterised by decreased levels of protein C and a rapidly progressive purpuric rash, often leading to ischaemia, amputations and death.
CASE SUMMARY
A previously healthy 66-year-old man presented with a vasculitic rash and abdominal pain following exposure to naproxen (NSAID), which quickly deteriorated to purpura fulminans-like eruption and skin necrosis, mainly involving the face and hands. The presence of IgA sediments on skin biopsy and decreased levels of complement as well as protein C pointed to an immune-mediated inflammatory process. Dramatic clinical escalation with immediate risk to organs and life required an aggressive and broad-spectrum therapeutic approach in an intensive care setting. Clinical improvement and complete reconstitution of protein C were achieved following plasma exchange with fresh frozen plasma (FFP) and immunosuppression with glucocorticoids with no persistent organ damage.
CONCLUSIONS
This rare case illustrates the catastrophic cross links between NSAIDs, IgA-mediated hypersensitivity vasculitis and purpura fulminans-like syndrome. A high index of suspicion is required for the evaluation of environmental exposures such as drugs and infections in patients with vasculitis and/or purpura. A rapid and comprehensive therapeutic approach should be implemented to avoid multi-organ damage, amputations and death. Complete avoidance of the offending agent is key for future prevention of recurrence.
LEARNING POINTS
This case illustrates a rare cross link between a commonly used drug (NSAIDs) and severe, life-threatening hypersensitivity reactions (IgA vasculitis and purpura fulminans-like eruption).These events require a high index of suspicion and emphasise the importance of considering environmental exposures such as drugs in the immediate diagnosis of both conditions.In addition to long-term drug avoidance, early and aggressive interventions are required to avoid organ damage, amputations or death.
PubMed: 37920231
DOI: 10.12890/2023_004072 -
JAMA Dermatology Aug 2023Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe hypersensitivity reaction. Identifying a culprit drug is critical for patient care, yet...
IMPORTANCE
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe hypersensitivity reaction. Identifying a culprit drug is critical for patient care, yet identification is based on clinical judgment. Data are limited on the accuracy in or approach to identifying a culprit drug.
OBJECTIVE
To evaluate patient allergy list outcomes, current approaches in identifying culprit drugs, and potential methods of improving culprit drug identification.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study spanned 18 years (January 2000 to July 2018), was conducted at Brigham and Women's Hospital and Massachusetts General Hospital (Boston), and included patients with clinically and histologically confirmed cases of SJS/TEN overlap and TEN.
MAIN OUTCOMES AND MEASURES
This study descriptively analyzed potential culprits to SJS/TEN, patients' allergy lists, and currently used approaches that led to those lists. It then tested the theoretical contribution of incorporating various parameters to allergy list outcomes.
RESULTS
Of 48 patients (29 women [60.4%]; 4 Asian [8.3%], 6 Black [12.5%], 5 Hispanic [10.4%], and 25 White [52.1%] individuals; median age, 40 years [range, 1-82 years]), the mean (SD) number of drugs taken per patient at disease onset was 6.5 (4.7). Physicians labeled 17 patients as allergic to a single culprit drug. Comparatively, 104 drugs were added to allergy lists across all patients. Physicians' approaches relied largely on heuristic identification of high-notoriety drugs and the timing of drug exposure. Use of a vetted database for drug risk improved sensitivity. Algorithm for Drug Causality for Epidermal Necrolysis scoring was discordant in 28 cases, labeling an additional 9 drugs missed by physicians and clearing 43 drugs labeled as allergens by physicians. Human leukocyte antigen testing could have potentially affected 20 cases. Consideration of infection as a culprit was limited.
CONCLUSIONS AND RELEVANCE
The results of this cohort study suggest that currently used approaches to identify culprit drugs in SJS/TEN are associated with overlabeling patients allergic to likely nonculprit drugs and less commonly missed possible culprit drugs. Incorporation of a systematized unbiased approach could potentially improve culprit drug identification, although ultimately a diagnostic test is necessary.
Topics: Adult; Female; Humans; HLA Antigens; Retrospective Studies; Stevens-Johnson Syndrome; Male; Infant; Child, Preschool; Child; Adolescent; Young Adult; Middle Aged; Aged; Aged, 80 and over
PubMed: 37342052
DOI: 10.1001/jamadermatol.2023.1693 -
Journal of Clinical Medicine Mar 2024Fixed drug eruption (FDE) is a well-recognized, non-immediate, drug hypersensitivity reaction, often attributed to the use of various medications, most commonly... (Review)
Review
Fixed drug eruption (FDE) is a well-recognized, non-immediate, drug hypersensitivity reaction, often attributed to the use of various medications, most commonly non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Cross-reactivity between related NSAIDs in FDE has been reported, but among chemically unrelated NSAIDs, is rare. Herein, we present a rare well-documented case where a patient initially displayed tolerance to etoricoxib after experiencing a nimesulide-induced FDE. Subsequently, the patient developed an etoricoxib-induced FDE, accompanied by the development of bullous lesions. This case report and the literature review on comparable FDE occurrences shed light on the intricate nature of FDEs, suggesting the possibility of cross-reactivity between chemically related and unrelated NSAIDs or the emergence of new drug-specific T cells without cross-reactivity after multiple exposures to a drug in a susceptible patient. Our case underscores the importance of increased awareness and vigilance among both physicians and patients in the realm of personalized medicine. Further research is needed to unravel the intricate mechanisms behind these drug eruptions, improve diagnostic approaches, and enhance patient care.
PubMed: 38541809
DOI: 10.3390/jcm13061583 -
The Journal of Dermatology Sep 2023Decreased epidermal high-mobility group box 1 (HMGB1) expression is an early marker of epidermal injury in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)....
TNF-α induced extracellular release of keratinocyte high-mobility group box 1 in Stevens-Johnson syndrome/toxic epidermal necrolysis: Biomarker and putative mechanism of pathogenesis.
Decreased epidermal high-mobility group box 1 (HMGB1) expression is an early marker of epidermal injury in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Etanercept, an anti-tumor necrosis factor therapeutic, is effective in the treatment of SJS/TEN. The objective was to characterize antitumor necrosis factor-alpha (TNF-α)-mediated HMGB1 keratinocyte/epidermal release and etanercept modulation. HMGB1 release from TNF-α treated (± etanercept), or doxycycline-inducible RIPK3 or Bak-expressing human keratinocyte cells (HaCaTs) was determined by western blot/ELISA. Healthy skin explants were treated with TNF-α or serum (1:10 dilution) from immune checkpoint inhibitor-tolerant, lichenoid dermatitis or SJS/TEN patients ± etanercept. Histological and immunohistochemical analysis of HMGB1 was undertaken. TNF-α induced HMGB1 release in vitro via both necroptosis and apoptosis. Exposure of skin explants to TNF-α or SJS/TEN serum resulted in significant epidermal toxicity/detachment with substantial HMGB1 release which was attenuated by etanercept. Whole-slide image analysis of biopsies demonstrated significantly lower epidermal HMGB1 in pre-blistered SJS/TEN versus control (P < 0.05). Keratinocyte HMGB1 release, predominantly caused by necroptosis, can be attenuated by etanercept. Although TNF-α is a key mediator of epidermal HMGB1 release, other cytokines/cytotoxic proteins also contribute. Skin explant models represent a potential model of SJS/TEN that could be utilized for further mechanistic studies and targeted therapy screening.
Topics: Humans; Stevens-Johnson Syndrome; Tumor Necrosis Factor-alpha; Etanercept; HMGB1 Protein; Keratinocytes; Necrosis; Biomarkers
PubMed: 37269158
DOI: 10.1111/1346-8138.16847 -
International Journal of Trichology 2023Graham-Little-Piccardi-Lasseur syndrome (GLPLS) is characterized by diffuse alopecia and a lichenoid follicular eruption affecting the scalp, eyebrows, and...
Graham-Little-Piccardi-Lasseur syndrome (GLPLS) is characterized by diffuse alopecia and a lichenoid follicular eruption affecting the scalp, eyebrows, and intertriginous regions. It is considered a variant of lichen planopilaris. The condition often begins as hyperkeratotic papules on the trunk and extremities followed by the development of alopecia. Several subtypes of lichen planus have been associated with a photodistriubuted eruption including lichenoid drug reactions, actinic lichen planus, and lichen planus pigmentosus; however, there are no reported cases associated with GLPLS. We herein report the first case of GLPLS displaying a photodistributed lichenoid eruption to expand upon the differential diagnosis of photoaggravated conditions. We also use this case to review the pathophysiology and therapeutic modalities to manage GLPLS.
PubMed: 38765727
DOI: 10.4103/ijt.ijt_47_22 -
Cureus Nov 2023A new quinolone antibiotic called garenoxacin was developed in Japan. Garenoxacin is known to produce cutaneous adverse effects, particularly fixed drug eruption in...
A new quinolone antibiotic called garenoxacin was developed in Japan. Garenoxacin is known to produce cutaneous adverse effects, particularly fixed drug eruption in Japan, despite several reports of cutaneous adverse events in English-language literature. However, English-language literature has not yet reported that fixed drug eruption is a common clinical manifestation of garenoxacin-induced drug eruption. In this article, we present a case of multiple fixed drug eruptions and review the literature on case reports of drug eruptions caused by garenoxacin.
PubMed: 38084197
DOI: 10.7759/cureus.48596 -
Cureus Nov 2023Pruritus, colloquially known as itch, is a common clinical symptom seen in a variety of dermatological conditions and systemic disorders. Pruritus can broadly be...
Pruritus, colloquially known as itch, is a common clinical symptom seen in a variety of dermatological conditions and systemic disorders. Pruritus can broadly be classified into four categories: neuropathic, neurogenic/systemic, psychogenic, and pruritoceptive. Initial categorization depends on anatomical and pathophysiological aspects of presentation and is reflective of underlying etiology. We report a case of an 83-year-old man presenting with generalized pruritus secondary to cholestasis from bile duct malignancy. This case is notable for atypical presenting features, including a trunk eruption comprised of excoriated papules with onset following meloxicam initiation, mimicking a cutaneous adverse drug reaction. Providers should consider systemic etiologies of pruritus in patients presenting with cutaneous eruptions with atypical features. Accurate categorization of pruritus can facilitate treatment and/or additional investigation of systemic disease.
PubMed: 38116363
DOI: 10.7759/cureus.49049